Traumatic injury and hypovolemic shock are leading causes of death in children worldwide. Rapid, large volume crystalloid infusion and positive intrathoracic pressure ventilation resuscitation strategies often increase morbidity and mortality following hemorrhage. Augmenting negative intrathoracic pressure, even without fluid resuscitation, improves hemodynamic parameters and outcome in adult porcine hemorrhagic shock. Vascular biology, physiology, and tissue injury mechanisms change as the child matures from infancy through adolescence, and are distinctly different from adults. The optimal method to restore intravascular volume, prevent secondary organ damage, and prevent progression of reversible shock to irreversible circulatory collapse following severe blood loss in children is no known. Our central hypothesis is that use of intrathoracic pressure regulation (IPR), enhances negative intrathoracic pressure and thus will augment preload, improve cardiac output, enhance cerebral oxygenation, and delay or prevent the progression of reversible shock to irreversible circulatory collapse for infants and children. IPR therapy works by regulating intrathoracic pressures in non-breathing patients. It lowers intrathoracic pressures to subatmospheric levels (-5 to -12 cmH2O) after each positive pressure ventilation. Lowering intrathoracic pressure draws venous blood back to the heart and lowers intracranial pressure, thereby increasing systemic and cerebral perfusion. Cerebral perfusion is increased by decreased intracranial resistance to forward blood flow secondary to higher cardiac output. This novel therapy uses an external vacuum source to lower intrathoracic pressure and a switch to allow for intermittent positive pressure ventilation, as needed. The negative intrathoracic pressure is carefully titrated to optimize benefit with no evidence of harm to date. Building upon the successful Phase 1 studies that demonstrated improved 24 hour neurological survival when utilizing IPR technology in a pediatric porcine hemorrhage model, we propose to evaluate this innovative therapy in a carefully controlled clinical study in the pediatric population and measure key physiological variables including brain tissue oxygen levels. Specifically, the investigators propose to: 1) complete the development of and 510k clear an enhanced, miniaturized pediatric specific version of IPR therapy with variable vacuum levels that is housed in the expiratory limb of a standard ventilation circuit to be utilized in a clinical study, and 2) demonstrate proof of concep that application of intrathoracic pressure regulation (IPR) therapy will result in an increase in cardiac index in pediatric patients: a) with sepsis or b) who have undergone cardiac surgery for congenital heart disease (CHD) (single ventricle or tetralogy of Fallot). IPR resuscitation strategy has the potential to successfully combat hypovolemic shock and circulatory collapse, the most common cause of morbidity and mortality in children worldwide.